Up-regulation of soluble Axl and Mer receptor tyrosine kinases negatively correlates with Gas6 in established multiple sclerosis lesions

Jason G. Weinger, Kakuri M. Omari, Kurt Marsden, Cedric S. Raine, Bridget Shafit-Zagardo

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Multiple sclerosis is a disease that is characterized by inflammation, demyelination, and axonal damage; it ultimately forms gliotic scars and lesions that severely compromise the function of the central nervous system. Evidence has shown previously that altered growth factor receptor signaling contributes to lesion formation, impedes recovery, and plays a role in disease progression. Growth arrest-specific protein 6 (Gas6), the ligand for the TAM receptor tyrosine kinase family, consisting of Tyro3, Axl, and Mer, is important for cell growth, survival, and clearance of debris. In this study, we show that levels of membrane-bound Mer (205 kd), soluble Mer (⌈150 kd), and soluble Axl (80 kd) were all significantly elevated in homogenates from established multiple sclerosis lesions comprised of both chronic active and chronic silent lesions. Whereas in normal tissue Gas6 positively correlated with soluble Axl and Mer, there was a negative correlation between Gas6 and soluble Axl and Mer in established multiple sclerosis lesions. In addition, increased levels of soluble Axl and Mer were associated with increased levels of mature ADAM17, mature ADAM10, and Furin, proteins that are associated with Axl and Mer solubilization. Soluble Axl and Mer are both known to act as decoy receptors and block Gas6 binding to membrane-bound receptors. These data suggest that in multiple sclerosis lesions, dysregulation of protective Gas6 receptor signaling may prolong lesion activity.

Original languageEnglish (US)
Pages (from-to)283-293
Number of pages11
JournalAmerican Journal of Pathology
Volume175
Issue number1
DOIs
StatePublished - Jul 2009

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Multiple Sclerosis
Up-Regulation
Furin
Membranes
Growth Factor Receptors
Receptor Protein-Tyrosine Kinases
Demyelinating Diseases
Protein Binding
Cicatrix
Disease Progression
Cell Survival
Central Nervous System
growth arrest-specific protein 6
axl receptor tyrosine kinase
Ligands
Inflammation
Growth

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Up-regulation of soluble Axl and Mer receptor tyrosine kinases negatively correlates with Gas6 in established multiple sclerosis lesions. / Weinger, Jason G.; Omari, Kakuri M.; Marsden, Kurt; Raine, Cedric S.; Shafit-Zagardo, Bridget.

In: American Journal of Pathology, Vol. 175, No. 1, 07.2009, p. 283-293.

Research output: Contribution to journalArticle

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